The Ia antigens, usually expressed primarily on B lymphocytes, are found on a small percentage of normal peripheral blood T cells (average 2.6% by fluorescence and 10.8% by rosette assay). Elevated levels up to 40% by both assays were observed in a high proportion of patients with rheumatoid arthritis. Increases also were found in patients with systemic lupus erythematosus and various types of infections. The increases were evident with a specific heteroantiserum, a hybridoma reagent, and DR specific alloantisera. Normal levels were present in multiple sclerosis and an assortment of metabolic and other disorders. A rise in similarly positive T cells occurred in normal individuals after immunization with tetanus toxoid or PPD. The cells primarily involved in all of these instances were small lymphocytes, which stained relatively weakly with the fluorescent reagents and were readily distinguishable from T-cell blasts. They were found to be enriched in isolated T gamma fractions but were also found in other T cells. The accumulated evidence indicated that these cells represent an expansion of one or more subsets of T cells found in normal individuals, and that their level in the peripheral blood may serve as an index of immunological stimulation.